The present invention relates to a solid preparation for dialysis for use in preparing a dialysate containing sodium bicarbonate. That is, the present invention relates to a solid preparation containing electrolytes, an acid and a sugar, which is to be used in sodium bicarbonate solid preparations for dialysis which usually comprise two preparations. These are a preparation containing sodium bicarbonate in addition to a preparation containing electrolytes, an acid, and a sugar and not containing sodium bicarbonate (hereinafter referred to as a double preparation type sodium bicarbonate solid preparation for dialysis).
When hemodialysis is carried out for a patient having decreased kidney function, the blood of the patient is purified in an artificial kidney. A dialysate is perfused inside of this artificial kidney, and waste products in the blood are generally transferred into the dialysate through a dialysis membrane. As this dialysate, acetic acid-containing dialysate has widely been used. In recent years, however, it has been substituted by a dialysate using sodium bicarbonate that remarkably reduces discomfort during the hemodialysis.
The dialysate containing sodium bicarbonate is usually prepared from two kinds of dialysate preparations, one being a liquid preparation containing electrolyte components (for example, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and sodium acetate) and a pH adjusting agent (for example, acetic acid) (hereinafter referred to as liquid A preparation), and the other being a liquid preparation containing sodium bicarbonate (hereinafter referred to as liquid B preparation). The dialysate preparations sometimes contain a sugar such as glucose, or another preparation containing a sugar is mixed with these dialysate preparations.
The liquid A preparation and the liquid B preparation have hitherto been sold in the form of dense liquids prepared at a predetermined concentration, and users have diluted them with water for use. However, since about 300 liters of a dialysate is needed for one patient for one dialysis, in the case of conducting dialysis treatments for many patients, a large quantity of a dense liquid is used, and dilution of it with water is needed. Thus, in order to relieve a burden on people who prepare a dialysate, and to save space, cases using a B preparation that is pulverized have increased. A double preparation type sodium bicarbonate solid preparation for dialysis in which the A preparation is also pulverized has also been recently developed.
As a pulverized double preparation type sodium bicarbonate solid preparation for dialysis, a preparation for dialysis that comprises two compositions, that is, one powdery preparation (A preparation) comprising electrolytes (except for sodium bicarbonate), glucose and a liquid acid, and another powdery preparation (B preparation) comprising only sodium bicarbonate, or sodium bicarbonate and sodium acetate or glucose, has been disclosed (Japanese Patent Publication No. 2749375 and No. 2751933, and Japanese Patent Unexamined Publication No. Hei 3-38527).
Among these preparations for dialysis, either a dry method or a fluidized bed method is used to produce the A preparation. The dry method comprises stirring and mixing electrolytes except for sodium bicarbonate and glucose using a stirring mixer, subsequently pulverizing the mixture using a pulverizer, after that mixing the mixture again, and after granulating the mixture using a dry granulator, mixing the granulated mixture with a liquid acid. Moreover, the fluidized bed method comprises mixing sodium chloride and glucose using a stirring mixer, and, after granulating the mixture while spraying the mixture in a fluidized bed granulator with an aqueous solution obtained by dissolving electrolytes except for sodium chloride and sodium bicarbonate into water, mixing them with a liquid acid.
However, in a preparation for dialysis that is obtained by the methods described above, glucose is likely to be decomposed or colored because time for heating glucose during the production process is long. Thus it has been generally considered that a double preparation type sodium bicarbonate solid preparation for dialysis in which the A preparation contains glucose has a shortened period of time for maintaining stability as compared with a sodium bicarbonate solid preparation for dialysis comprising three preparations where glucose is separately provided. Furthermore, it is difficult to achieve content homogeneity in a double preparation type sodium bicarbonate solid preparation for dialysis that is obtained by the methods described above.
In view of the above circumstances, it is an object of the present invention to provide a solid preparation for dialysis containing electrolytes (except for sodium bicarbonate), an acid and a sugar. The preparation can maintain stability equal to a sodium bicarbonate solid preparation for dialysis comprising three preparations where a sugar is separately provided, is excellent in content homogeneity and there is no fear that the sugar is decomposed or colored.
In order to solve the above problems, the present inventors wholeheartedly investigated. They found out that the desired object can be achieved by granulating a composition containing electrolytes except for sodium bicarbonate and a composition containing a sugar separately and subsequently mixing them with an acid to produce an A preparation of a double preparation type sodium bicarbonate solid preparation for dialysis, and attained the present invention.
That is, the present invention is a solid preparation for dialysis comprising a mixture of particles of a first composition containing one or more electrolytes selected from the group consisting of sodium chloride, calcium chloride, magnesium chloride, potassium chloride and sodium acetate, particles of a second composition containing a sugar and one or more electrolytes selected from the group consisting of sodium chloride, calcium chloride, magnesium chloride, potassium chloride and sodium acetate, and an acid.
Further, the present invention is a process for producing a solid preparation for dialysis comprising the following steps (1) to (3):
(1) a step of spraying an aqueous solution containing one or more electrolytes selected from the group consisting of calcium chloride, magnesium chloride, potassium chloride and sodium acetate onto core particles containing sodium chloride, and drying the coated particles to obtain a first composition;
(2) a step of spraying an aqueous solution containing one or more electrolytes selected from the group consisting of sodium chloride, calcium chloride, magnesium chloride, potassium chloride and sodium acetate onto core particles containing a sugar, and drying the coated particles to obtain a second composition; and
(3) a step of mixing the first composition obtained in step (1) and the second composition obtained in step (2), and further mixing them with an acid to obtain the solid preparation for dialysis.
Moreover, the present invention is a process for producing a solid preparation for dialysis comprising the following steps (1) to (3):
(1) a step of spraying an aqueous solution containing one or more electrolytes selected from the group consisting of calcium chloride, magnesium chloride, potassium chloride and sodium acetate onto core particles containing sodium chloride, and drying the coated particles to obtain a first composition;
(2) a step of spraying an aqueous solution containing one or more electrolytes selected from the group consisting of sodium chloride, calcium chloride, magnesium chloride, potassium chloride and sodium acetate onto core particles containing a sugar, and drying the coated particles to obtain a second composition; and
(3) a step of mixing an acid with the first composition obtained in step (1), and subsequently mixing the resultant mixture with the second composition obtained in step (2) to obtain the solid preparation for dialysis.